Post-Translational Modifications in Tau and Their Roles in Alzheimer's Pathology

IF 1.8 4区医学 Q3 CLINICAL NEUROLOGY

Current Alzheimer research Pub Date : 2024-04-16 DOI:10.2174/0115672050301407240408033046

Subha Kalyaanamoorthy, Stanley Kojo Opare, Xiaoxiao Xu, Aravindhan Ganesan, Praveen P.N. Rao

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Abstract

:: Microtubule-Associated Protein Tau (also known as tau) has been shown to accumulate into paired helical filaments and neurofibrillary tangles, which are known hallmarks of Alzheimer’s disease (AD) pathology. Decades of research have shown that tau protein undergoes extensive post-translational modifications (PTMs), which can alter the protein's structure, function, and dynamics and impact the various properties such as solubility, aggregation, localization, and homeostasis. There is a vast amount of information describing the impact and role of different PTMs in AD pathology and neuroprotection. However, the complex interplay between these PTMs remains elusive. Therefore, in this review, we aim to comprehend the key post-translational modifications occurring in tau and summarize potential connections to clarify their impact on the physiology and pathophysiology of tau. Further, we describe how different computational modeling methods have helped in understanding the impact of PTMs on the structure and functions of the tau protein. Finally, we highlight the tau PTM-related therapeutics strategies that are explored for the development of AD therapy.

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Tau 的翻译后修饰及其在阿尔茨海默病病理学中的作用

::微管相关蛋白 Tau（又称 tau）已被证明会积聚成成对螺旋丝和神经纤维缠结，这是已知的阿尔茨海默病（AD）病理特征。数十年的研究表明，tau 蛋白会经历大量的翻译后修饰（PTM），这些修饰会改变蛋白质的结构、功能和动力学，并影响其各种特性，如溶解性、聚集性、定位和稳态。有大量信息描述了不同的 PTMs 在艾滋病病理和神经保护中的影响和作用。然而，这些 PTM 之间复杂的相互作用仍然难以捉摸。因此，在这篇综述中，我们旨在理解发生在 tau 中的关键翻译后修饰，并总结其潜在联系，以阐明它们对 tau 生理和病理生理学的影响。此外，我们还介绍了不同的计算建模方法如何帮助理解 PTM 对 tau 蛋白结构和功能的影响。最后，我们重点介绍了为开发注意力缺失症疗法而探索的 tau PTM 相关治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Alzheimer research 医学-神经科学

CiteScore

4.00

自引率

4.80%

发文量

审稿时长

4-8 weeks

期刊介绍： Current Alzheimer Research publishes peer-reviewed frontier review, research, drug clinical trial studies and letter articles on all areas of Alzheimer’s disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer’s disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer’s disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer''s disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer’s disease. Current Alzheimer Research provides a comprehensive ''bird''s-eye view'' of the current state of Alzheimer''s research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.